MyMedR

Displaying publications 1 - 20 of 47 in total

Abstract:

Sort:

Morbidity and treatment costs of cystic fibrosis in a middle-income country

Hng SY, Thinakaran AS, Ooi CJ, Eg KP, Thong MK, Tae SK, et al.

Singapore Med J, 2023 Sep 19.
PMID: 37870036 DOI: 10.4103/singaporemedj.SMJ-2022-093

INTRODUCTION: : Asian children with cystic fibrosis (CF) managed in Malaysia have significant morbidity with limited access to life-sustaining treatments. We determined the morbidity and treatment cost of CF in a resource-limited country.
METHODS: This cross-sectional study included all children diagnosed with CF in our centre. Data on clinical presentation, genetic mutation, serial spirometry results and complications were collected. Out-of-pocket (OOP) and healthcare costs over 1 year were retrieved for patients who were alive. Cohen's d and odds ratio (OR) were used to determine the effect size.
RESULTS: Twenty-four patients were diagnosed with CF. Five patients died at a median (range) age of 18 (0.3-22) years. F508deletion (c. 1521_1523delCTT) was found in 20% of the alleles, while 89% of the variants were detected in nine patients. Body mass index (BMI) Z score was >-1.96 in 70.6% of patients. Two thirds (68%) were colonised with Pseudomonas aeruginosa, and this was associated with lower weight (P = 0.009) and BMI (P = 0.02) Z scores. Only 18% had FEV1 Z scores >-1.96. Early symptom onset (d = 0.74), delayed diagnosis (d = 2.07), a low FEF25-75 Z score (d = 0.82) and a high sweat conductance (d = 1.19) were associated with death. Inpatient cost was mainly from diagnostic tests, while medications contributed to half of the outpatient cost.
Healthcare utilisation cost was catastrophic, amounting to 20% of the total income.
CONCLUSION: Asian children with CF suffer significant complications such as low weight, low lung function and shortened lifespan. P. aeruginosa colonisation was frequent and associated with poor growth. Healthcare cost to parents was catastrophic.
Serosurveillance of SARS-CoV-2 in companion animals in Sarawak, Malaysia

Tan CS, Bandak DB, Habeebur-Rahman SP, Tan LT, Lim LLA

Virol J, 2023 Aug 07;20(1):176.
PMID: 37550752 DOI: 10.1186/s12985-023-02133-9

SARS-CoV-2 is a zoonotic betacoronavirus that was first reported at the dawn of 2019 in Wuhan, China and has since spread globally, causing an ongoing pandemic. Anthroponotic transmission was reported early, with confirmed infections reported in 26 species to date, including dogs and cats. However, there is a paucity of reports on the transmission of SARS-CoV-2 to companion animals, and thus, we aimed to estimate the seroprevalence of SARS-CoV-2 in dogs and cats in Sarawak, Malaysia. From August 2022 to 2023, we screened plasma samples of 172 companion animals in Sarawak, Malaysia, using a species-independent surrogate virus neutralization test. Our findings revealed the presence of neutralizing antibodies of SARS-CoV-2 in 24.5% (27/110) of dogs and 24.2% (15/62) of cats. To the best of our knowledge, this is the first report of the seroprevalence of SARS-CoV-2 in companion animals in Malaysia. Our findings emphasize the need for pet owners to distance themselves from their pets when unwell, and a strategy must be in place to monitor SARS-CoV-2 in companion animals to assess the potential impact of the virus on companion animals.
Fulltext A Keystone Gut Bacterium Christensenella minuta-A Potential Biotherapeutic Agent for Obesity and Associated Metabolic Diseases

Ang WS, Law JW, Letchumanan V, Hong KW, Wong SH, Ab Mutalib NS, et al.

Foods, 2023 Jun 26;12(13).
PMID: 37444223 DOI: 10.3390/foods12132485

A new next-generation probiotic, Christensenella minuta was first discovered in 2012 from healthy human stool and described under the phylum Firmicutes. C. minuta is a subdominant commensal bacterium with highly heritable properties that exhibits mutual interactions with other heritable microbiomes, and its relative abundance is positively correlated with the lean host phenotype associated with a low BMI index. It has been the subject of numerous studies, owing to its potential health benefits. This article reviews the evidence from various studies of C. minuta interventions using animal models for managing metabolic diseases, such as obesity, inflammatory bowel disease, and type 2 diabetes, characterized by gut microbiota dysbiosis and disruption of host metabolism. Notably, more studies have presented the complex interaction between C. minuta and host metabolism when it comes to metabolic health. Therefore, C. minuta could be a potential candidate for innovative microbiome-based biotherapy via fecal microbiota transplantation or oral administration. However, the detailed underlying mechanism of action requires further investigation.
Fulltext The Emerging Role of MMP12 in the Oral Environment

Lin B, Ser HL, Wang L, Li J, Chan KG, Lee LH, et al.

Int J Mol Sci, 2023 Feb 28;24(5).
PMID: 36902078 DOI: 10.3390/ijms24054648

Matrix metalloproteinase-12 (MMP12), or macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation. Recent reports show MMP12 has been implicated in the pathogenesis of periodontal diseases. To date, this review represents the latest comprehensive overview of MMP12 in various oral diseases, such as periodontitis, temporomandibular joint dysfunction (TMD), orthodontic tooth movement (OTM), and oral squamous cell carcinoma (OSCC). Furthermore, the current knowledge regarding the distribution of MMP12 in different tissues is also illustrated in this review. Studies have implicated the association of MMP12 expression with the pathogenesis of several representative oral diseases, including periodontitis, TMD, OSCC, OTM, and bone remodelling. Although there may be a potential role of MMP12 in oral diseases, the exact pathophysiological role of MMP12 remains to be elucidated. Understanding the cellular and molecular biology of MMP12 is essential, as MMP12 could be a potential target for developing therapeutic strategies targeting inflammatory and immunologically related oral diseases.
Fulltext Psychological Symptoms in COVID-19 Patients: Insights into Pathophysiology and Risk Factors of Long COVID-19

Thye AY, Law JW, Tan LT, Pusparajah P, Ser HL, Thurairajasingam S, et al.

Biology (Basel), 2022 Jan 02;11(1).
PMID: 35053059 DOI: 10.3390/biology11010061

There is growing evidence of studies associating COVID-19 survivors with increased mental health consequences. Mental health implications related to a COVID-19 infection include both acute and long-term consequences. Here we discuss COVID-19-associated psychiatric sequelae, particularly anxiety, depression, and post-traumatic stress disorder (PTSD), drawing parallels to past coronavirus outbreaks. A literature search was completed across three databases, using keywords to search for relevant articles. The cause may directly correlate to the infection through both direct and indirect mechanisms, but the underlying etiology appears more complex and multifactorial, involving environmental, psychological, and biological factors. Although most risk factors and prevalence rates vary across various studies, being of the female gender and having a history of psychiatric disorders seem consistent. Several studies will be presented, demonstrating COVID-19 survivors presenting higher rates of mental health consequences than the general population. The possible mechanisms by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the brain, affecting the central nervous system (CNS) and causing these psychiatric sequelae, will be discussed, particularly concerning the SARS-CoV-2 entry via the angiotensin-converting enzyme 2 (ACE-2) receptors and the implications of the immune inflammatory signaling on neuropsychiatric disorders. Some possible therapeutic options will also be considered.
Fulltext Streptomyces sp.-A Treasure Trove of Weapons to Combat Methicillin-Resistant Staphylococcus aureus Biofilm Associated with Biomedical Devices

Pusparajah P, Letchumanan V, Law JW, Ab Mutalib NS, Ong YS, Goh BH, et al.

Int J Mol Sci, 2021 Aug 28;22(17).
PMID: 34502269 DOI: 10.3390/ijms22179360

Biofilms formed by methicillin-resistant S. aureus (MRSA) are among the most frequent causes of biomedical device-related infection, which are difficult to treat and are often persistent and recurrent. Thus, new and effective antibiofilm agents are urgently needed. In this article, we review the most relevant literature of the recent years reporting on promising anti-MRSA biofilm agents derived from the genus Streptomyces bacteria, and discuss the potential contribution of these newly reported antibiofilm compounds to the current strategies in preventing biofilm formation and eradicating pre-existing biofilms of the clinically important pathogen MRSA. Many efforts are evidenced to address biofilm-related infections, and some novel strategies have been developed and demonstrated encouraging results in preclinical studies. Nevertheless, more in vivo studies with appropriate biofilm models and well-designed multicenter clinical trials are needed to assess the prospects of these strategies.
Fulltext COVID-19: Insights into Potential Vaccines

Loo KY, Letchumanan V, Ser HL, Teoh SL, Law JW, Tan LT, et al.

Microorganisms, 2021 Mar 15;9(3).
PMID: 33804162 DOI: 10.3390/microorganisms9030605

People around the world ushered in the new year 2021 with a fear of COVID-19, as family members have lost their loved ones to the disease. Millions of people have been infected, and the livelihood of many has been jeopardized due to the pandemic. Pharmaceutical companies are racing against time to develop an effective vaccine to protect against COVID-19. Researchers have developed various types of candidate vaccines with the release of the genetic sequence of the SARS-CoV-2 virus in January. These include inactivated viral vaccines, protein subunit vaccines, mRNA vaccines, and recombinant viral vector vaccines. To date, several vaccines have been authorized for emergency use and they have been administered in countries across the globe. Meanwhile, there are also vaccine candidates in Phase III clinical trials awaiting results and approval from authorities. These candidates have shown positive results in the previous stages of the trials, whereby they could induce an immune response with minimal side effects in the participants. This review aims to discuss the different vaccine platforms and the clinical trials of the candidate vaccines.
Health-related quality of life and developmental outcome of children on home mechanical ventilation in a developing country: A cross-sectional study

Tan LT, Nathan AM, Jayanath S, Eg KP, Thavagnanam S, Lum LCS, et al.

Pediatr Pulmonol, 2020 12;55(12):3477-3486.
PMID: 33002341 DOI: 10.1002/ppul.25083

BACKGROUND: Provision of home mechanical ventilation (HMV) to children with chronic respiratory insufficiency enhances growth and quality of life. The hypothesis was that health-related quality of life (HRQoL) and the development of these children were poorer than in healthy children.
OBJECTIVES: To determine the HRQoL and developmental outcome of children on HMV.
METHODS: This cross-sectional study used the TNO-AZL Preschool children's Quality Of Life (TAPQOL; <5 years old) and Health Utilities Index (HUI) 2/3 (≥5 years old) to assess the quality of life and the Schedule of Growing Skills-II to assess development. Instruments were used on children currently or previously on HMV (≥3 months) and compared with age and sex-matched controls.
RESULTS: Sixty-five patients and 130 controls were recruited. Patients' median (interquartile range) age was 3.12 (1.65, 5.81) years. Patients had significantly lower TAPQOL scores in the domains of lung, liveliness, positive mood, social functioning, motor functioning, and communication, and lower HUI 2/3 scores in hearing, sensation, pain, speech, mobility, ambulatory, dexterity, and self-care domains. The developmental outcome of patients was poorer in all domains. However, patients had fewer behavioral problems. Those with respiratory tract disease and without comorbidities had better HRQoL and developmental scores. Having a parent as the primary caregiver was associated with better speech and language skills.
CONCLUSIONS: HRQoL and the developmental outcome are lower in children on HMV compared to controls. Children with respiratory tract disease and without comorbidities have a better outcome. Parents play a crucial role in the acquisition of speech.
Fulltext Anticancer Drug Discovery from Microbial Sources: The Unique Mangrove Streptomycetes

Law JW, Law LN, Letchumanan V, Tan LT, Wong SH, Chan KG, et al.

Molecules, 2020 Nov 17;25(22).
PMID: 33212836 DOI: 10.3390/molecules25225365

Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; however, there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals. This suggested the importance of the prompt detection, effective treatment, and prevention strategies. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites. Streptomycetes from mangrove environments attract researchers' attention due to their ability to synthesize diverse, interesting bioactive metabolites. The present review highlights research on mangrove-derived streptomycetes and the production of anticancer-related compounds from these microorganisms. Research studies conducted between 2008 and 2019, specifically mentioning the isolation of streptomycetes from mangrove areas and described the successful purification of compound(s) or generation of crude extracts with cytotoxic activity against human cancer cell lines, were compiled in this review. It is anticipated that there will be an increase in prospects for mangrove-derived streptomycetes as one of the natural resources for the isolation of chemotherapeutic agents.
Fulltext Exploring the Role of Gut Bacteria in Health and Disease in Preterm Neonates

Lee JK, Hern Tan LT, Ramadas A, Ab Mutalib NS, Lee LH

Int J Environ Res Public Health, 2020 09 23;17(19).
PMID: 32977611 DOI: 10.3390/ijerph17196963

The mortality rate of very preterm infants with birth weight <1500 g is as high as 15%. The survivors till discharge have a high incidence of significant morbidity, which includes necrotising enterocolitis (NEC), early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS). More than 25% of preterm births are associated with microbial invasion of amniotic cavity. The preterm gut microbiome subsequently undergoes an early disruption before achieving bacterial maturation. It is postulated that bacterial gut colonisation at birth and postnatal intestinal dysbacteriosis precede the development of NEC and LONS in very preterm infants. In fact, bacterial colonization patterns in preterm infants greatly differ from term infants due to maternal chorioamnionitis, gestational age, delivery method, feeding type, antibiotic exposure and the environment factor in neonatal intensive care unit (NICU). In this regard, this review provides an overview on the gut bacteria in preterm neonates' meconium and stool. More than 50% of preterm meconium contains bacteria and the proportion increases with lower gestational age. Researchers revealed that the gut bacterial diversity is reduced in preterm infants at risk for LONS and NEC. Nevertheless, the association between gut dysbacteriosis and NEC is inconclusive with regards to relative bacteria abundance and between-sample beta diversity indices. With most studies show a disruption of the Proteobacteria and Firmicutes preceding the NEC. Hence, this review sheds light on whether gut bacteria at birth either alone or in combination with postnatal gut dysbacteriosis are associated with mortality and the morbidity of LONS and NEC in very preterm infants.
Fulltext Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis?

Chew SS, Tan LT, Law JW, Pusparajah P, Goh BH, Ab Mutalib NS, et al.

Cancers (Basel), 2020 Aug 13;12(8).
PMID: 32823729 DOI: 10.3390/cancers12082272

Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
Fulltext Streptomyces sp. Strain MUSC 125 from Mangrove Soil in Malaysia with Anti-MRSA, Anti-Biofilm and Antioxidant Activities

Mangzira Kemung H, Tan LT, Chan KG, Ser HL, Law JW, Lee LH, et al.

Molecules, 2020 Aug 03;25(15).
PMID: 32756432 DOI: 10.3390/molecules25153545

There is an urgent need to search for new antibiotics to counter the growing number of antibiotic-resistant bacterial strains, one of which is methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report a Streptomyces sp. strain MUSC 125 from mangrove soil in Malaysia which was identified using 16S rRNA phylogenetic and phenotypic analysis. The methanolic extract of strain MUSC 125 showed anti-MRSA, anti-biofilm and antioxidant activities. Strain MUSC 125 was further screened for the presence of secondary metabolite biosynthetic genes. Our results indicated that both polyketide synthase (pks) gene clusters, pksI and pksII, were detected in strain MUSC 125 by PCR amplification. In addition, gas chromatography-mass spectroscopy (GC-MS) detected the presence of different chemicals in the methanolic extract. Based on the GC-MS analysis, eight known compounds were detected suggesting their contribution towards the anti-MRSA and anti-biofilm activities observed. Overall, the study bolsters the potential of strain MUSC 125 as a promising source of anti-MRSA and antibiofilm compounds and warrants further investigation.
Fulltext Density of breast: An independent risk factor for developing breast cancer, a prospective study at two premium breast centers

Lo CH, Chai XY, Ting SSW, Ang SC, Chin X, Tan LT, et al.

Cancer Med, 2020 05;9(9):3244-3251.
PMID: 32130790 DOI: 10.1002/cam4.2821

BACKGROUND: Breast cancer is the leading cause of death among women worldwide. Studies have identified breast density as a controversial risk factor of breast cancer. Moreover, studies found that breast density reduction through Tamoxifen could reduce risk of breast cancer significantly. To date, no study on the association between breast density and breast cancer has been carried out in Malaysia. If breast density is proven to be a risk factor of breast cancer, intervention could be carried out to reduce breast cancer risk through breast density reduction.
PURPOSE: To determine if density of breast is an independent risk factor which will contribute to development of breast cancer.
MATERIALS AND METHODS: A prospective cohort study is carried out in two hospitals targeting adult female patients who presented to the Breast Clinic with symptoms suspicious of breast cancer. Participants recruited were investigated for breast cancer based on their symptoms. Breast density assessed from mammogram was correlated with tissue biopsy results and final diagnosis of benign or malignant breast disease.
RESULTS: Participants with dense breasts showed 29% increased risk of breast cancer when compared to those with almost entirely fatty breasts (odds ratio [OR] 1.29, 95% CI 0.38-4.44, P = .683). Among the postmenopausal women, those with dense breasts were 3.1 times more likely to develop breast cancer compared with those with fatty breasts (OR 3.125, 95% CI 0.72-13.64, P = .13). Moreover, the chance of developing breast cancer increases with age (OR 1.046, 95% CI 1.003-1.090, P
Overexpression of oxyR Increases Phenazine-1-Carboxylic Acid Biosynthesis via Small RNA phrS in the Rhizobacterium Strain Pseudomonas PA1201

Sun S, Tan LT, Fang YL, Jin ZJ, Zhou L, Goh BH, et al.

Mol Plant Microbe Interact, 2020 Mar;33(3):488-498.
PMID: 31710580 DOI: 10.1094/MPMI-09-19-0264-R

Phenazine-1-carboxylic acid (PCA) is the primary active component in the newly registered, commercial biopesticide Shenqinmycin and is produced during fermentation by the engineered rhizobacterium strain Pseudomonas PA1201. Both phz1 and phz2 gene clusters contribute to PCA biosynthesis. In this study, we evaluated the role of OxyR in the regulation of PCA biosynthesis in PA1201. We first showed a functional link between oxyR expression and PCA biosynthesis. Deletion of oxyR and overexpression of oxyR both increase PCA biosynthesis. The molecular mechanisms underlying OxyR regulation of PCA production were investigated using several approaches. OxyR acts divergently in phz1 and phz2. Overexpression of oxyR activated the expression of phz1 and phz1-dependent PCA production. However, overexpression of oxyR had little effect on phz2-dependent PCA biosynthesis, while deletion of oxyR promoted phz2-dependent PCA production and exerted a negative effect on phz2 expression. Further, OxyR directly bound to the phz2 promoter region. In addition, the regulation of PCA biosynthesis by OxyR was associated with quorum sensing (QS) systems. Overexpression of OxyR positively regulated pqs QS system. Finally, transcriptomic analysis and subsequent genetic analysis revealed the small RNA phrS plays a key role in OxyR-dependent PCA accumulation. Specifically, OxyR directly binds to the phrS promoter region to positively regulate phrS expression wherein PhrS regulates the PCA positive regulator MvfR in order to control PCA biosynthesis.
Fulltext Effect of (R)-salbutamol on the switch of phenotype and metabolic pattern in LPS-induced macrophage cells

Wang S, Liu F, Tan KS, Ser HL, Tan LT, Lee LH, et al.

J Cell Mol Med, 2020 01;24(1):722-736.
PMID: 31680470 DOI: 10.1111/jcmm.14780

Evidence demonstrates that M1 macrophage polarization promotes inflammatory disease. Here, we discovered that (R)-salbutamol, a β2 receptor agonist, inhibits and reprograms the cellular metabolism of RAW264.7 macrophages. (R)-salbutamol significantly inhibited LPS-induced M1 macrophage polarization and downregulated expressions of typical M1 macrophage cytokines, including monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α). Also, (R)-salbutamol significantly decreased the production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and reactive oxygen species (ROS), while increasing the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. In contrast, (S)-salbutamol increased the production of NO and ROS. Bioenergetic profiles showed that (R)-salbutamol significantly reduced aerobic glycolysis and enhanced mitochondrial respiration. Untargeted metabolomics analysis demonstrated that (R)-salbutamol modulated metabolic pathways, of which three metabolic pathways, namely, (a) phenylalanine metabolism, (b) the pentose phosphate pathway and (c) glycerophospholipid metabolism were the most noticeably impacted pathways. The effects of (R)-salbutamol on M1 polarization were inhibited by a specific β2 receptor antagonist, ICI-118551. These findings demonstrated that (R)-salbutamol inhibits the M1 phenotype by downregulating aerobic glycolysis and glycerophospholipid metabolism, which may propose (R)-salbutamol as the major pharmacologically active component of racemic salbutamol for the treatment of inflammatory diseases and highlight the medicinal value of (R)-salbutamol.
Fulltext Antioxidant Activities of Streptomyces sp. strain MUSC 14 from Mangrove Forest Soil in Malaysia

Kemung HM, Tan LT, Chan KG, Ser HL, Law JW, Lee LH, et al.

Biomed Res Int, 2020;2020:6402607.
PMID: 32258133 DOI: 10.1155/2020/6402607

The mangrove ecosystem of Malaysia remains yet to be fully explored for potential microbes that produce biologically active metabolites. In the present study, a mangrove-derived Streptomyces sp. strain MUSC 14 previously isolated from the state of Pahang, Malaysia Peninsula, was studied for its potential in producing antioxidant metabolites. The identity of Streptomyces sp. strain MUSC14 was consistent with the genotypic and phenotypic characteristics of the Streptomyces genus. The antioxidant potential of Streptomyces sp. strain MUSC 14 was determined through screening of its methanolic extract against sets of antioxidant assays. The results were indicative of Streptomyces sp. strain MUSC 14 displaying strong antioxidant activity against ABTS, DPPH free radicals and metal chelating activity of 62.71 ± 3.30%, 24.71 ± 2.22%, and 55.82 ± 2.35%, respectively. The result of ferric reducing activity measured in terms of dose was equivalent to 2.35-2.45 μg of positive control ascorbic acid. Furthermore, there was a high correlation between the total phenolic content and the antioxidant activities with r = 0.979, r = 0.858, and r = 0.983 representing ABTS, DPPH, and metal chelation, respectively. Overall, the present study suggests that Streptomyces sp. strain MUSC 14 from mangrove forest soil has potential to produce antioxidant metabolites that can be further exploited for therapeutic application.
An unusual cause of acute abdomen and acute renal failure: Djenkolism

Sumitro K, Yong CS, Tan LT, Choo S, Lim CY, Shariman H, et al.

Malays Fam Physician, 2020;15(2):50-52.
PMID: 32843946

The djenkol bean (Archidendron pauciflorum) is a native delicacy in Southeast Asia, though consumption can sometimes lead to djenkolism. Clinical features of djenkolism include acute abdominal pain, hematuria, urinary retention, and acute kidney injury (AKI). The pain can be severe, which often leads to a misdiagnosis of acute abdomen. In this paper, we report the case of an Indonesian migrant with djenkolism. Due to the short history and severity of the abdominal pain, medical professionals suspected acute abdomen and proceeded with a negative exploratory laparotomy. However, djenkolism was suspected once relatives informed the professionals that the patient had consumed djenkol beans hours earlier. The patient recovered through aggressive hydration and urine alkalinization with bicarbonate infusion. We highlight the importance of being aware of this rare cause of AKI, especially in Southeast Asia, in order to provide early diagnoses and prompt treatments.
Fulltext Streptomyces sp. MUM256: A Source for Apoptosis Inducing and Cell Cycle-Arresting Bioactive Compounds against Colon Cancer Cells

Tan LT, Chan CK, Chan KG, Pusparajah P, Khan TM, Ser HL, et al.

Cancers (Basel), 2019 Nov 06;11(11).
PMID: 31698795 DOI: 10.3390/cancers11111742

New and effective anticancer compounds are much needed as the incidence of cancer continues to rise. Microorganisms from a variety of environments are promising sources of new drugs; Streptomyces sp. MUM256, which was isolated from mangrove soil in Malaysia as part of our ongoing efforts to study mangrove resources, was shown to produce bioactive metabolites with chemopreventive potential. This present study is a continuation of our previous efforts and aimed to investigate the underlying mechanisms of the ethyl acetate fraction of MUM256 crude extract (MUM256 EA) in inhibiting the proliferation of HCT116 cells. Our data showed that MUM256 EA reduced proliferation of HCT116 cells via induction of cell-cycle arrest. Molecular studies revealed that MUM256 EA regulated the expression level of several important cell-cycle regulatory proteins. The results also demonstrated that MUM256 EA induced apoptosis in HCT116 cells mediated through the intrinsic pathway. Gas chromatography-mass spectrometry (GC-MS) analysis detected several chemical compounds present in MUM256 EA, including cyclic dipeptides which previous literature has reported to demonstrate various pharmacological properties. The cyclic dipeptides were further shown to inhibit HCT116 cells while exerting little to no toxicity on normal colon cells in this study. Taken together, the findings of this project highlight the important role of exploring the mangrove microorganisms as a bioresource which hold tremendous promise for the development of chemopreventive drugs against colorectal cancer.
Fulltext Streptomyces sp. MUM273b: A mangrove-derived potential source for antioxidant and UVB radiation protectants

Tan LT, Mahendra CK, Yow YY, Chan KG, Khan TM, Lee LH, et al.

Microbiologyopen, 2019 10;8(10):e859.
PMID: 31199601 DOI: 10.1002/mbo3.859

Microbial natural products serve as a good source for antioxidants. The mangrove-derived Streptomyces bacteria have been evidenced to produce antioxidative compounds. This study reports the isolation of Streptomyces sp. MUM273b from mangrove soil that may serve as a promising source of antioxidants and UV-protective agents. Identification and characterization methods determine that strain MUM273b belongs to the genus Streptomyces. The MUM273b extract exhibits antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging activities and also metal-chelating activity. The MUM273b extract was also shown to inhibit the production of malondialdehyde in metal-induced lipid peroxidation. Strong correlation between the antioxidant activities and the total phenolic content of MUM273b extract was shown. In addition, MUM273b extract exhibited cytoprotective effect on the UVB-induced cell death in HaCaT keratinocytes. Gas chromatography-mass spectrometry analysis detected phenolics, pyrrole, pyrazine, ester, and cyclic dipeptides in MUM273b extract. In summary, Streptomyces MUM273b extract portrays an exciting avenue for future antioxidative drugs and cosmeceuticals development.
Fulltext Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer Chemoprevention

Goh JXH, Tan LT, Goh JK, Chan KG, Pusparajah P, Lee LH, et al.

Cancers (Basel), 2019 Jun 21;11(6).
PMID: 31234411 DOI: 10.3390/cancers11060867

The search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents against cancer. One of the promising compounds under extensive research is nobiletin (NOB), a polymethoxyflavone (PMF) extracted exclusively from citrus peel. Not only does nobiletin itself exhibit anti-cancer properties, but its derivatives are also promising chemopreventive agents; examples of derivatives with anti-cancer activity include 3'-demethylnobiletin (3'-DMN), 4'-demethylnobiletin (4'-DMN), 3',4'-didemethylnobiletin (3',4'-DMN) and 5-demethylnobiletin (5-DMN). In vitro studies have demonstrated differential efficacies and mechanisms of NOB and its derivatives in inhibiting and killing of colon cancer cells. The chemopreventive potential of NOB has also been well demonstrated in several in vivo colon carcinogenesis animal models. NOB and its derivatives target multiple pathways in cancer progression and inhibit several of the hallmark features of colorectal cancer (CRC) pathophysiology, including arresting the cell cycle, inhibiting cell proliferation, inducing apoptosis, preventing tumour formation, reducing inflammatory effects and limiting angiogenesis. However, these substances have low oral bioavailability that limits their clinical utility, hence there have been numerous efforts exploring better drug delivery strategies for NOB and these are part of this review. We also reviewed data related to patents involving NOB to illustrate the extensiveness of each research area and its direction of commercialisation. Furthermore, this review also provides suggested directions for future research to advance NOB as the next promising candidate in CRC chemoprevention.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links